Atos homolog protein B (or ATOSB), is a protein that, in humans, is encoded by the ATOSB gene (previously denoted FAM214B). Not much has been reported about the function of the protein, but it is predicted to act as a transcription regulator.
The protein has 538 amino acids. The gene contain 9 exon. There has been studies that there are low expression of this gene in patients with major depression disorder. In most organisms such as mammals, amphibians, reptiles, and birds, there are high levels of gene expression in the bone marrow and blood. For humans in fetal development, FAM214B is mostly expressed in the brains and bone marrow. Gene
Aliases This is also known as KIAA1539, BA182N22.6, FLJ11560, PI.11659_5, LOC80256, and RP11-182N22.6.
Location FAM214B is located on human chromosome 9 at the locus position 9p13.3. The gene is 12,229 bp long and it is at position 35,104,112 bp to the 35,116,341 on chromosome 9.
Transcript variants There are currently 2 mRNA transcripts variants of FAM214B. Variant 1 encodes the longest transcript and Variant 2 differs in the 5' UTR. +Table 1. Known human mRNA transcript variants for FAM214BNameAccession numberNumber of ExonsSize (bp)Transcript Variant 1NM_001317991.293124Transcript Variant 2NM_025182.492999
Protein
Isoforms There are currently 2 isoforms for FAM214B protein, where isoform 1 encodes for Variant 1 for the longest protein and isoform 2 encoded by Variant 2.
+Table 2. Known human protein isoforms for FAM214BNameAccession numberSize (AA)Isoform 1NP_001304920.1 538Isoform 2NP_079458.2 514
Composition and characteristics The FAM214B protein has a predicted molecular weight of 56.7 kDa and has an isometric point of 9.1. For protein composition, the FAM214B protein contains high amounts of Glycine and Proline, while there was a lack of Isoleucine. There were clusters of positively charged regions on amino acid position 308 to 327 which composed of mostly Leucine and Arginine. There was a repetitive structure of amino acids GPGLG repeat on amino acid position 82 to 86, and 106 to 110. There were repeats of amino acids of Proline in position 10 to 25, and 225 to 265.
Protein domain The FAM214B contains a DUF4210 domain of unknown function at the position 348 to 402, and a chromosome segregation domain at position 480 to 536. The DUF4210 domain is currently has unknown function and predicted to be necessary for chromosome segregation in meiosis.
Secondary structure Using Phyre2, Ali2D, and I-TASSER predicted that the FAM214B secondary structure composed of mostly beta sheets and one alpha helix. Phyre2 prediction is shown on the right.
Tertiary structure Tertiary Structure was predicted using I-Tasser where the purple represents the C-terminal and the red represents the N-terminal shown on the right.
Post-translation modifications
Phosphorylation There are 7 predicted phosphorylation sites on the FAM214B protein which consists of mostly serine and threonine residues.
+Table 3. Predicted phosphorylation sites in FAM214B protein PositionAmino Acid119Serine240Tyrosine323Serine477Tyrosine491Serine494Serine508Serine
Sub-cellular localization Studies of FAM214B protein was determined that the protein is localized in the nucleus.
Expression and regulation
Promoters
Using the Genomatix Gene2Promoter tool, it was determined that the FAM214B has 5 promoters that are found in Homo sapiens. The promoter GXP_38326 has the highest number of encoded transcripts which spans on position 35115811 to 35116911 on the negative strand of human chromosome 9.
+Table 4. Promoters for FAM214B genePromoter IDStart PositionEnd PositionLength (bp)OrientationNumber of transcripts supportedGXP_900372935111384351126101227 - strand4GXP_443618335112353351133921040 - strand1GXP_3832635115811351169111101- strand9GXP_900373035116054351170931040- strand1GXP_443618435116302351174771176- strand1
Transcription factors
The table represents a list of predicted transcription factors that bind to the GXP_9003729 promoter using Genomatix MatInspector tool.
+Table 5. Predicted transcription factors binding to GXP_9003729Matrix FamilyDetail Family InfoMatrixDetailed Matrix InfoV$LEFFLEF1/TCFV$LEF1.02TCF/LEF-1, involved in the Wnt signal transduction pathwayV$HOXFParalog hox genes 1-8 from the four hox clusters A, B, C, DV$NANOG.01Homeobox transcription factor NanogV$TCFFTCF11 transcription factorV$TCF11.01TCF11/LCR-F1/Nrf1 homodimersV$PEROPeroxisome proliferator-activated receptorV$PPAR_RXR.01PPAR/RXR heterodimers, DR1 sitesV$BCDFBicoid-like homeodomain transcription factorsV$PTX1.01Pituitary Homeobox 1 (Ptx1, Pitx-1)V$RUSHSWI/SNF related nucleophosphoproteins with a RING finger DNA binding motifV$SMARCA3.01SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 3V$ZF42C2H2 zinc finger transcription factors 42V$ZNF692.01Zinc finger protein 692 (AICAR responsive element binding protein - AREBP)V$EGRFEGR/nerve growth factor induced protein C & related factorsV$WT1.02Wilms Tumor SuppressorV$SAL4Spalt-like transcription factor 4V$SALL4.01Spalt like 4, DRRS, HSAL4, ZNF797V$PAX3PAX-3 binding sitesV$PAX3.03Pax-3 paired domain proteinV$MZF1Myeloid zinc finger 1 factorsV$MZF1.02Myeloid zinc finger protein MZF1V$GATAGATA binding factorsV$GATA1.01GATA-binding factor 1V$AP1RMAF and AP1 related factorsV$MARE_ARE.01Antioxidant response elementsV$TAIPTGF-beta induced apoptosis proteinsV$CSRNP1.01Cysteine-serine-rich nuclear protein 1 (AXUD1, AXIN1 up-regulated 1)V$STATSignal transducer and activator of transcriptionV$STAT5B.01Signal transducer and activator of transcription 5BV$ZF03C2H2 zinc finger transcription factors 3V$ZNF217.01Zinc finger protein 217V$BRNFBrn POU domain factorsV$BRN2.03Brn-2, POU-III protein classV$GRHLGrainyhead-like transcription factorsV$GRHL1.01Grainyhead-like 1 (LBP32, MGR, TFCP2L2)V$PEROPeroxisome proliferator-activated receptorV$PPARG.02Peroxisome proliferator-activated receptor gammaV$E2FFE2F-myc activator/cell cycle regulatorV$E2F.01E2F, involved in cell cycle regulation, interacts with Rb p107 protein
Expression
Tissue specific expression The RNA-Seq data from NCBI gene and The Human Atlas Protein shows that the FAM214B is highly expressed in the bone marrow, placenta, esophagus, and the brain such as corpus callosum, pons and medulla, and spinal cord.
Embryonic development An in-situ hybridization technique has been conducted on mouse embryos that shows high levels of FAM214B transcript in the hippocampus and neocortex.
Differential expression There has been numerous experiments on levels of expression for FAM214B. Patients with diabetic nephropathy express higher levels of FAM214B gene than those who are normal. Patients with bipolar disorders expressed higher levels of FAM214B in the orbitofrontal cortex than those who are normal. Patients with allergic nasal epithelium responses to house dust mites have lower expression of FAM214B than those who did not have allergies to house mites.
3'UTR
There are 9 stem loops and miRNAs that bind to FAM214B transcript 3'UTR shown on the right.
Interacting proteins
A list of proteins that interact with FAM214B in IntAct and UniProt database.
+Table 6. List of proteins that interact with FAM214BProteinDescriptionIKZF1DNA-binding protein IkarosTRIM27Zinc finger protein RFPFHL5Four and a half LIM domains protein 5CEP70Centrosomal protein of 70 kDaTRAF4TNF receptor-associated factor 4KIF20AKinesin-like protein KIF20AMDFIMyoD family inhibitorCYSRT1Cysteine-rich tail protein 1MYO1FUnconventional myosin-IfEYA2Eyes absent homolog 2
Homology and evolution
Orthologs and paralogs FAM214B has orthologs in Mammalia, Aves, Reptilia, Amphibia, Actinopterygii, Arthropodas, Ascomycota, Zygomycota, and Plantae. There is one paralog that is FAM214A. The FAM214A protein has 1076 amino acids and is located on chromosome 13.
+Table 6. List of Homo Sapiens FAM214B orthologsGenus and speciesCommon nameTaxonomic groupDate of Divergence (MYA)Accession numberNumber of Amino AcidsIdentityMus musculusMouseRodenta90NP_001240282.1 53891%Chrysemys picta belliiPainted turtleTestudines312XP_005311754.1 64645%Gallus gallusChickenGalliformes312XP_004937179.1 60646%Nanorana parkeriHimalaya frogAnura351XP_018429110.170241%Acipenser ruthenusSterletAcipenseriformes435XP_033861969.2 62341%Sarcoptes scabieiItch miteSarcoptes797KAF7489920.187147%Entomophthora muscaeFly fungusEntomophthoraceae1105KAF7753830.1 45533%Mikania micranthaBitter vineAsterales1496KAD4889130.1 60128%
Evolutionary history
The most distant species relating to humans was Mikania micrantha which was about 1496 MYA. The most closely related relative for this gene found in mammals comparing to humans was the mouse which was dated about 90 MYA. The FAM214B is conserved in Eukaryota. In terms of the molecular clock analysis, it seems that FAM214B has evolved quicker than Cytochrome c but much slower than Fibrinogen alpha.
Studies of clinical significance There are studies that show the gene expression of KIAA1539 in patients with major depression disorders by using biomarkers to detect vulnerability to recurrent depression. Low expression of this gene was common in patients who have MDD and was significantly difference than those who did not have MDD. Experiments were conducted in patients with major depression disorders by using biomarkers to detect vulnerability to recurrent depression and is expressed in patients with depressive disorders before and after cognitive behavioral therapy.
References